The effect produced by repeated administration of the H1-antihistaminics diphenhydramine, promethazine and pyrilamine on their ability to induce antinociception was evaluated in the mouse hot-plate and abdominal constriction tests. Contrary to morphine, baclofen and oxotremorine, the three H1 antagonists investigated did not promote the development of tolerance to the analgesic effect after 14 days of repeated treatment. H1 antagonists could, therefore, represent a promising pharmacological approach to the management of chronic pain.